Alzheimer’s Prevention

Hello and welcome to Nutrition Facts – the podcast that brings you the latest in evidence-based nutrition research.  I’m your host, Dr. Michael Greger.

I’m often asked what my opinion is about one food or another.  I know what people are asking but, you know, I’m not interested in opinions.  I’m not interested in beliefs.  I’m interested in the science.  What does the best available balance of evidence published in the peer-reviewed medical literature show right now?  That’s why I wrote my book, “How Not to Die”, and why I created my nonprofit site NutritionFacts.org and, now, this podcast.

Today we’re going to talk about a disease that is taking a massive toll on our population, Alzheimer’s, which now affects millions of Americans.  

Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks.

In most people with Alzheimer’s, symptoms first appear in their mid-60s, but there is new evidence that suggests the disease may gain a foothold even earlier.

In 1985, a Swiss pathologist noted Alzheimer’s disease-like changes (plaques and tangles) in the brains of about three-quarters of a small group of men and women in their 50s and 60s who had died from other causes, whereas most brains collected under age 30 were clean, but these studies just involved a few dozen people.

Based on thousands of autopsies, one can see what appears to be the first silent stages starting even in our 20s in about 10% of the population, and about 50% by age 50.  Just as the first malignant cells in cancer fail to produce any clinically detectable symptoms, but represent a larger and more potentially life-threatening disease process, the presence of these tangles in the brain may constitute a true threat.

The high prevalence of the first stage of the disease, even in the young, and its extraordinarily long duration, most people don’t get diagnosed with Alzheimer’s until their 70s, had not been fully appreciated until now.  We now understand that neurodegenerative brain changes begin by middle age and so does cognitive decline.  We start losing brain function in our 40s.

Before people are diagnosed with Alzheimer’s, they’re diagnosed with what’s called MCI, mild cognitive impairment.  That’s when cognitive decline becomes clinically apparent.  A few years later, Alzheimer’s may be diagnosed, which then results in death, but we never knew what was happening before mild cognitive impairment was diagnosed, until now.  There appears to be a slow decline in brain function and the buildup of plaques and tangles in the brain for decades before Alzheimer’s is diagnosed.

This finding potentially has profound implications for the prevention of dementia–we have to start early, before marked brain loss has occurred.

The good news is that brain disease is not inevitable, even after age 100.  Oldest woman in the world retained the brainpower of those practically half her age.  Had she not died from stomach cancer, she could have kept on thriving.

It turns out there’s no such thing as dying from old age.  Forty-two thousand consecutive autopsies were studied and centenarians (those living past 100), though most were perceived to have been healthy just prior to death, even by their physicians, succumbed to diseases in 100% of the cases examined.  Not one died of old age.  Until recently, you know, advanced age was considered kind of a disease in and of itself, but people don’t die as a consequence of old age, as commonly assumed, but from diseases, most commonly, heart attacks. 

High-tech advances, such as PET scanning, offer new insights into the role cholesterol plays in both the amyloid cascade and vascular models of the development of Alzheimer’s dementia.  Here’s more information.

Millions suffer from Alzheimer’s disease and the available and foreseeable treatments are disappointing at best.  Given the absence of disease-modifying treatments, there has been growing interest in effective strategies for the prevention of the disease in the first place.  Even if we are able to just delay the onset by as little as one year, we could potentially prevent more than 9 million cases over the next 40 years.

Once cognitive functions are lost in Alzheimer’s disease patients, they may be lost forever.  Consequently, prevention, rather than a cure for Alzheimer’s disease, appears a more realistic strategy to offset the catastrophic impact of this dementia.

Considerable evidence now indicates that Alzheimer’s disease is primarily a vascular disorder, based on a number of lines of evidence that point toward impaired circulation of blood to the brain.

Vascular risk factors, such as high cholesterol, can be thought of as a ticking time bomb to Alzheimer’s disease.  What’s bad for the heart may be bad for the mind.

Traditionally, there have been two competing theories for the cause of Alzheimer’s–the amyloid cascade model that implicates the buildup of amyloid plaques within the brain and the vascular model, that argues that it is the lack of adequate blood flow to the brain due to atherosclerosis.  We now realize they are not mutually exclusive, and that arterial disease can set up a vicious cycle, in which atherosclerotic plaques in the arteries may contribute to Alzheimer’s plaques in the brain.

Although, at times, portrayed as tantamount to poison, cholesterol is an essential structural component of all our cells, that is why our body makes it, but if there’s too much, it can become a major factor contributing to various diseases, including coronary heart disease, stroke, and neurodegenerative diseases, like Alzheimer’s.  Too much cholesterol in our blood is unanimously recognized to be a risk factor for the development Alzheimer’s disease, and cholesterol may play an active role in the progression of Alzheimer’s as well.

Autopsy studies have found that Alzheimer’s brains have significantly more cholesterol than normal brains and it specifically appears to accumulate in the Alzheimer brain plaques, but we used to think the pool of cholesterol in the brain was separate from the pool we had in our blood, but there is now growing evidence to the contrary.  For example, LDL may be able to cross the blood–brain barrier into the brain.  So, a high-fat diet may not only increase cholesterol levels in the blood, but also the influx of cholesterol into the central nervous system.

In addition, having high cholesterol may even damage the blood-brain barrier itself and allow for even more cholesterol to flow into the brain, providing the missing link between high cholesterol and Alzheimer’s. Individuals with high cholesterol levels at midlife have a higher risk of going on to develop Alzheimer’s disease.  A cholesterol over 250 could potentially triple the odds of Alzheimer’s.

And now we have high-tech PET scanning of the brain that can directly correlate the amount of so-called bad cholesterol in our blood with the amount of amyloid build up in our brain.  You can do it right in a Petri dish–adding cholesterol makes them churn out more amyloid that makes up Alzheimer plaques, whereas removing cholesterol can decrease the level of amyloid released from cells.

In addition, amyloid degradation is less efficient, clearing amyloid is less efficient in a high-cholesterol environment.  Cholesterol can then help seed the clumping of the amyloid.  Using an electron microscope, you can see the clustering of amyloid fibers on and around little microcrystals of cholesterol. 

Once in the brain, cholesterol can also undergo auto-oxidation, causing the formation of highly toxic free radicals.  So, having high cholesterol levels in the blood is thought to increase the risk of dementia, not only by inducing atherosclerosis and impairing blood flow, but may directly affect the neurodegeneration within the brain.  

In conclusion, excess dietary cholesterol could, in principle, contribute to the development of Alzheimer’s disease and the evidence linking high cholesterol to Alzheimer’s appears to be steadily mounting.

Of course, some of this work was paid for by drug companies hoping to capitalize on Alzheimer’s with cholesterol-lowering statin drugs–ironic, since statins themselves can cause cognitive impairment.  Though rare, statin side effects may include short- and long-term memory loss, behavioral changes, impaired concentration and attention, paranoia, anxiety, as early as five days after starting the drugs, but sometimes even months later, though folks should recover within a month of stopping the drugs.

A better strategy then may be to change the lifestyle factors that lead to the high cholesterol in the first place, in particular, reducing saturated fat from the diet, but it’s not enough for us to just tell our individual patients.  Systematic implementation of education campaigns promoting radical changes in cultural and societal values may be necessary to adopt Alzheimer’s-defeating strategies by patients in a broader sense and such actions may provide potentially huge dividends by preventing both cardiovascular disease and dementia–two of our leading causes of death.

Rural India has the lowest validated Alzheimer’s rates in the world.  So, we had to ask:  Is it due to the turmeric in their curry or their largely plant-based diets?  Here are the results of those studies. 

There are anti-inflammatory drugs that may reduce the risk of Alzheimer’s disease, but stomach, liver and kidney toxicity precludes their widespread use.  So, maybe using an anti-inflammatory food, like the spice turmeric found in curry powder, could offer the benefits without the risks.  Before even considering putting it to the test though, one might ask:  Well, do populations that eat a lot of turmeric have a lower prevalence of dementia?  They may actually have the lowest reported prevalence of dementia in Alzheimer’s.  Okay.  So far, so good, but maybe because it is such an impoverished area that people just don’t live very long.  So, you need to know more than just prevalence, how many Alzheimer’s cases are walking around, but the incidence of the disease, how many new people are coming down with it every year, which reflects the kind of true rate of disease occurrence.

In rural Pennsylvania, the incidence rate of Alzheimer’s disease among seniors is 19.  Nineteen people in a thousand over age 65 develop Alzheimer’s every year in rural Pennsylvania.  In rural India, using the same diagnostic criteria, that same rate is 3, confirming they have among the lowest reported Alzheimer’s rates in the world. 

Although there isn’t much to go on, the lower prevalence of Alzheimer’s in India is generally attributed to the turmeric consumption as a part of curry and it is assumed that people who use turmeric regularly have a lower incidence of the disease, but let’s not just assume.

A thousand people tested and those who consumed curry, at least occasionally, did do better on simple cognitive tests than those that didn’t.  Those that ate curry often had only about half the odds of showing cognitive impairment, after adjusting for a wide variety of potential confounding factors.  This suggests that curry consumption may be associated with better cognitive performance.

Of course, it probably matters what’s being curried; are we talking chicken masala, or Chana masala, with chickpeas instead of chicks?  It may be no coincidence that the country with among the lowest rates of Alzheimer’s has among the lowest rates of meat consumption, with a significant chunk of the population eating meat-free and egg-free diets.

We’ve known for over 20 years now, that those who eat meat (red meat or white meat) appear between two to three times more likely to become demented compared to vegetarians and the longer one eats meat-free, the lower the associated risk of dementia, whether or not you curry-favor with your brain.

Here’s more information about treating people who already have Alzheimer’s with the spice turmeric.

An exciting case series was published in 2012.  Three Alzheimer’s patients treated with turmeric and their symptoms declined, along with the burden on their caregivers.  Let me show you what these data mean in real lives.  Case number one:  83-year-old woman, started losing her memory, getting disoriented.  Then, she started having problems taking care of herself, wandering aimlessly, incontinent.  After the turmeric though, her agitation, apathy, anxiety, and irritability were relieved, she had less accidents.  Furthermore, she began to laugh again, and sing again, and knit again.  After taking turmeric for more than a year, she came to recognize her family and now lives a peaceful life without a significant behavioral or psychological symptom of dementia.

Case 2 was similar, but with hallucinations and delusions and depression, which appeared relieved by turmeric.  She began to recognize her family again and now lives in a peacefully serene manner and, the third case, similar as well, including an improvement in cognition–the first demonstration that turmeric may be effective and safe for the treatment of the behavioral and psychological symptoms of dementia in Alzheimer’s disease patients.  

They call it a drug, but it’s just a spice you can walk into any grocery store and buy for a few bucks.  They were giving people like a teaspoon a day, which comes out to be about 15 cents.

Two trials using curcumin supplements, rather than turmeric, however, failed to show a benefit.  Curcumin is just one of hundreds of phytochemicals found in turmeric.  Concentrated into pill form at up to 40 times the dose, no evidence of efficacy was found.  Why didn’t they get the same dramatic results we saw in the three case reports?  Well, those three cases may have been total flukes, but on the other hand, turmeric, the whole food, is greater than the sum of its parts.

There is a long list of compounds that have been isolated from turmeric and it’s possible that each component in the mixture of curcumin-like compounds plays the distinct role in making it useful in Alzheimer’s disease and, hence, a mixture of compounds might better represent turmeric in its medicinal value better than curcumin alone.  But why concoct some artificial mixture when Mother Nature already did it for us with turmeric?  Because you can’t patent the spice and if you can’t patent it, how are you going to charge more than 15 cents?

This is the kind of information that you may not hear about elsewhere, because there is no corporate budget driving its promotion, but we’re not funded by drug companies or food companies, but by listeners and viewers like you. 

Everything on our website is free.  There’s no ads, no corporate sponsorship.  It’s strictly non-commercial.  I’m not selling anything.  I just put it up as a public service, as a labor of love, as a tribute to my grandmother, whose own life was saved with evidence-based nutrition.

To see any graphs, charts, graphics, images, or studies mentioned here, please go to the Nutrition Facts podcast landing page.  There, you’ll find all the videos I highlighted with links to all the sources cited.

Thanks for listening to Nutrition Facts.  I’m Dr. Michael Greger.